Abstract
Blast formation and mitotic activation of G0-arrested mouse thymocytes were triggered by the addition of concanavalin A plus interleukin 2 (IL-2) to the culture medium. When added alone, Con A induces within 6 hr a complex reprogramming ("priming") that comprises the activation of the IL-2 receptor gene. The primed thymocytes are competent to interact with IL-2 and to respond to its growth-promoting effect, which corresponds to blast formation and mitotic activation. Cyclosporin A, an immunosuppressive cyclic peptide of fungal origin, prevents in T lymphocytes the activation of a set(s) of genes encoding lymphokines and the IL-2 receptor but does not affect their expression once they have been activated. The biomedical implications of these observations are discussed.
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- Beveridge T. Clinical transplantation--overview. Prog Allergy. 1986;38:269–292. [PubMed] [Google Scholar]
- Block L. H., Siegenthaler W., Drews J. Inhibition of mitogen-induced lymphokine production by cyclosporin A. Klin Wochenschr. 1980 Jul 15;58(14):739–742. doi: 10.1007/BF01478462. [DOI] [PubMed] [Google Scholar]
- Bordier C. Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem. 1981 Feb 25;256(4):1604–1607. [PubMed] [Google Scholar]
- Borel J. F., Feurer C., Gubler H. U., Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976 Jul;6(4):468–475. doi: 10.1007/BF01973261. [DOI] [PubMed] [Google Scholar]
- Brack C., Mattaj I. W., Gautschi J., Cammisuli S. Cyclosporin A is a differential inhibitor of eukaryotic RNA polymerases. Exp Cell Res. 1984 Apr;151(2):314–321. doi: 10.1016/0014-4827(84)90382-3. [DOI] [PubMed] [Google Scholar]
- Cantrell D. A., Smith K. A. The interleukin-2 T-cell system: a new cell growth model. Science. 1984 Jun 22;224(4655):1312–1316. doi: 10.1126/science.6427923. [DOI] [PubMed] [Google Scholar]
- Ceredig R., Lowenthal J. W., Nabholz M., MacDonald H. R. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Nature. 1985 Mar 7;314(6006):98–100. doi: 10.1038/314098a0. [DOI] [PubMed] [Google Scholar]
- Dongworth D. W., Klaus G. G. Effects of cyclosporin A on the immune system of the mouse. I. Evidence for a direct selective effect of cyclosporin A on B cells responding to anti-immunoglobulin antibodies. Eur J Immunol. 1982 Dec;12(12):1018–1022. doi: 10.1002/eji.1830121207. [DOI] [PubMed] [Google Scholar]
- Elliott J. F., Lin Y., Mizel S. B., Bleackley R. C., Harnish D. G., Paetkau V. Induction of interleukin 2 messenger RNA inhibited by cyclosporin A. Science. 1984 Dec 21;226(4681):1439–1441. doi: 10.1126/science.6334364. [DOI] [PubMed] [Google Scholar]
- Farrar J. J., Fuller-Farrar J., Simon P. L., Hilfiker M. L., Stadler B. M., Farrar W. L. Thymoma production of T cell growth factor (Interleukin 2). J Immunol. 1980 Dec;125(6):2555–2558. [PubMed] [Google Scholar]
- Hess A. D., Tutschka P. J., Pu Z., Santos G. W. Effect of cyclosporin A on human lymphocyte responses in vitro. IV. Production of T cell stimulatory growth factors and development of responsiveness to these growth factors in CsA-treated primary MLR cultures. J Immunol. 1982 Jan;128(1):360–367. [PubMed] [Google Scholar]
- Khandjian E. W., Matter J. M., Léonard N., Weil R. Simian virus 40 and polyoma virus stimulate overall cellular RNA and protein synthesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1476–1480. doi: 10.1073/pnas.77.3.1476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Khandjian E. W. UV crosslinking of RNA to nylon membrane enhances hybridization signals. Mol Biol Rep. 1986;11(2):107–115. doi: 10.1007/BF00364822. [DOI] [PubMed] [Google Scholar]
- Krönke M., Leonard W. J., Depper J. M., Arya S. K., Wong-Staal F., Gallo R. C., Waldmann T. A., Greene W. C. Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214–5218. doi: 10.1073/pnas.81.16.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
- Matter J. M., Tiercy J. M., Weil R. Sequential stimulation of cellular RNA synthesis in polyoma-infected mouse kidney cell cultures. Nucleic Acids Res. 1983 Oct 11;11(19):6611–6629. doi: 10.1093/nar/11.19.6611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyawaki T., Yachie A., Ohzeki S., Nagaoki T., Taniguchi N. Cyclosporin A does not prevent expression of Tac antigen, a probable TCGF receptor molecule, on mitogen-stimulated human T cells. J Immunol. 1983 Jun;130(6):2737–2742. [PubMed] [Google Scholar]
- O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
- Palacios R. Cyclosporin A inhibits the proliferative response and the generation of helper, suppressor and cytotoxic T-cell functions in the autologous mixed lymphocyte reaction. Cell Immunol. 1981 Jul 1;61(2):453–462. doi: 10.1016/0008-8749(81)90393-2. [DOI] [PubMed] [Google Scholar]
- Palacios R., Möller G. Cyclosporin A blocks receptors for HLA-DR antigens on T cells. Nature. 1981 Apr 30;290(5809):792–794. doi: 10.1038/290792a0. [DOI] [PubMed] [Google Scholar]
- Peacock A. C., Dingman C. W. Molecular weight estimation and separation of ribonucleic acid by electrophoresis in agarose-acrylamide composite gels. Biochemistry. 1968 Feb;7(2):668–674. doi: 10.1021/bi00842a023. [DOI] [PubMed] [Google Scholar]
- Reem G. H., Cook L. A., Vilcek J. Gamma interferon synthesis by human thymocytes and T lymphocytes inhibited by cyclosporin A. Science. 1983 Jul 1;221(4605):63–65. doi: 10.1126/science.6407112. [DOI] [PubMed] [Google Scholar]
- Russell D. H., Matrisian L., Kibler R., Larson D. F., Poulos B., Magun B. E. Prolactin receptors on human lymphocytes and their modulation by cyclosporine. Biochem Biophys Res Commun. 1984 Jun 29;121(3):899–906. doi: 10.1016/0006-291x(84)90762-9. [DOI] [PubMed] [Google Scholar]
- Shevach E. M. The effects of cyclosporin A on the immune system. Annu Rev Immunol. 1985;3:397–423. doi: 10.1146/annurev.iy.03.040185.002145. [DOI] [PubMed] [Google Scholar]
- Shidani B., Milon G., Marchal G., Truffa-Bachi P. Cyclosporin A inhibits the delayed-type hypersensitivity reaction: impaired production of early pro-inflammatory mediator(s). Eur J Immunol. 1984 Apr;14(4):314–318. doi: 10.1002/eji.1830140407. [DOI] [PubMed] [Google Scholar]
- Shimuzu A., Kondo S., Takeda S., Yodoi J., Ishida N., Sabe H., Osawa H., Diamantstein T., Nikaido T., Honjo T. Nucleotide sequence of mouse IL-2 receptor cDNA and its comparison with the human IL-2 receptor sequence. Nucleic Acids Res. 1985 Mar 11;13(5):1505–1516. doi: 10.1093/nar/13.5.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith K. A., Baker P. E., Gillis S., Ruscetti F. W. Functional and molecular characteristics of T-cell growth factor. Mol Immunol. 1980 May;17(5):579–589. doi: 10.1016/0161-5890(80)90156-x. [DOI] [PubMed] [Google Scholar]
- Tiercy J. M., Weil R. Serum-induced stimulation of nucleoplasmic and nucleolar transcription in mouse 3T3 fibroblasts revisited. Eur J Biochem. 1983 Mar 1;131(1):47–55. doi: 10.1111/j.1432-1033.1983.tb07230.x. [DOI] [PubMed] [Google Scholar]
- Wiesinger D., Borel J. F. Studies on the mechanism of action of cyclosporin A. Immunobiology. 1980 Jan;156(4-5):454–463. doi: 10.1016/S0171-2985(80)80078-7. [DOI] [PubMed] [Google Scholar]